Nimesulide-SZ granules for preparation of suspension for oral use 100mg, 10pcs

Composition

1 package contains: Active ingredient: nimesulide – 100 mg; excipients: povidone K-30 (polyvinylpyrrolidone medium molecular weight) – 35.0 mg; lactose monohydrate (milk sugar) – 1663.0 mg; crospovidone (Collidone CL-M) – 120.0 mg; aspartame-10.0 mg;citric acid monohydrate-30.0 mg;orange flavor-42.0 mg

Pharmacological action

Nonsteroidal anti-inflammatory drugs (NSAIDs)ATX code:  M 01 AX 17 Pharmacodynamicanimesulide is a nonsteroidal anti-inflammatory drug from the class of sulfonamides. It has anti-inflammatory, analgesic and antipyretic effects. Unlike non-selective NSAIDs, nimesulide mainly inhibits cyclooxygenase-2( COX-2), inhibits prostaglandin synthesis in the inflammatory focus, and has a less pronounced inhibitory effect on cyclooxygenase-1 (COX-1). Pharmacokineticanimesulide is well absorbed from the gastrointestinal tract (GIT)The maximum concentration in blood plasma (Ctax) after oral use of a single dose of nimesulide,100 mg, is reached on average in 2-3 hours and is 3-4 mg/l. The area under the concentration-time curve (AUC) is 20-35 mg h/l. Binding to plasma proteins – up to 97.5%. It is metabolized in the liver by the cytochrome P450 (CYP)2C9 isoenzyme. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide-hydroxynimesulide, which is found exclusively in the form of glucuronate. Nimesulide is excreted mainly in the urine (about 50% of the dose taken), in the metabolized form, about 29% is excreted in the feces. The half-life (T 1/2) is 3.2-6 hours. The pharmacokinetic profile of nimesulide in the elderly and in patients with mild to moderate renal insufficiency does not change with the use of single and multiple/repeated doses. In a study conducted in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), the Cmax of nimesulide and its main metabolite was not higher than in healthy volunteers. AUC and T 1/2 were 50% higher, but within the range of AUC and Tj/2 values observed in healthy volunteers with nimesulide. Repeated use did not result in accumulation of nimesulide.

Indications

-acute pain (back pain, low back pain; musculoskeletal pain, including bruises, sprains and dislocations of joints; tendinitis, bursitis; toothache);- symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome; – primary algodismenorrhea. The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use; nimesulide is recommended for therapy as a second-line drug.

Use during pregnancy and lactation

Like other NSAID drugs that inhibit prostaglandin synthesis, nimesulide can negatively affect the course of pregnancy and / or embryo development and can lead to premature closure of the ductus arteriosus, hypertension in the fetal pulmonary artery system, impaired renal function, which can lead to renal failure with oliguria in the fetus, an increased risk of bleeding, reduced uterine contractility, and peripheral edema in the mother. The data obtained in the course of epidemiological studies indicate a possible increase in the risk of spontaneous abortion, the risk of heart disease and gastroschisis when using agents that block prostaglandin synthesis in the early stages of pregnancy. The absolute risk of developing an abnormality of the cardiovascular system increases from about 1% to 1.5%. It is believed that the risk increases with increasing dose and duration of use. Data on the penetration of nimesulide into breast milk are not available. The use of Nimesulide during pregnancy and lactation is contraindicated. The use of nimesulide may negatively affect female fertility and is not recommended for women planning pregnancy. When planning a pregnancy, you should consult your doctor.

Contraindications

– hypersensitivity to nimesulide or to other components of the drug;- hyperergic reactions in anamnesis (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other NSAIDs, including nimesulide;- complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose or paranasal sinuses with intolerance to acetylsalicylic acid and other NSAIDs (including in history);- a history of hepatotoxic reactions to nimesulide; – concomitant use with other medicinal products with potential hepatotoxicity (for example, other NSAIDs);- chronic inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase; – the period after coronary artery bypass grafting; – febrile syndrome and acute respiratory viral infections;- suspected acute surgical pathology; – peptic ulcer of the stomach or duodenum in the acute phase; erosive and ulcerative lesions of the gastrointestinal tract; perforations or gastrointestinal bleeding in the anamnesis;- a history of cerebrovascular bleeding or other diseases associated with increased bleeding;- severe blood clotting disorders;- severe heart failure;- severe renal insufficiency (creatinine clearance;- alcoholism, drug addiction; – hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. With caution Arterial hypertension, diabetes mellitus, compensated heart failure, ischemic heart disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, peripheral arterial diseases, hemorrhagic diathesis, smoking, creatinine clearance 30-60 ml/min. A history of ulcerative lesions of the gastrointestinal tract; a history of infection caused by Helicobacter pylori; advanced age; long-term previous use of NSAIDs; severe somatic diseases. Concomitant use with the following medications: anticoagulants (e. g., warfarin), antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e. g., prednisone), selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline).

Side effects

Frequency is classified by category in accordance with the recommendations of the world health organization, depending on the event occurrence: very often (> 1/10), often (> 1/100, < 1/10), infrequently (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (<1/10000), vklyuchennye messages. Blood pressure and lymphatic system disorders: rarely-anemia, eosinophilia, hemorrhages; very rarely-thrombocytopenia, pancytopenia, thrombocytopenic purpura. Immune system disorders: rarely-hypersensitivity reactions; very rarely-anaphylactoid reactions. Skin and subcutaneous tissue disorders: infrequently-pruritus, skin rash, excessive sweating; rarely-dermatitis; very rarely-urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome). Nervous system disorders: infrequently – dizziness; very rarely-headache, drowsiness, encephalopathy (Reye’s syndrome). Mental disorders: rarely-feeling of fear, nervousness, night “nightmare” dreams. Visual disturbances: rarely – blurred vision. very rarely – visual impairment. Hearing disorders and labyrinth disorders: vertigo is very rare. Disorders of the cardiovascular system: infrequently-increased blood pressure; rarely-tachycardia, lability of blood pressure, “flushes” of blood to the skin of the face, palpitation sensation. Respiratory system disorders: infrequently-shortness of breath; very rarely-exacerbation of bronchial asthma, bronchospasm. Disorders of the gastrointestinal tract: often – diarrhea, nausea, vomiting; infrequently-constipation, flatulence, gastritis, gastrointestinal bleeding, ulceration and / or perforation of the stomach or duodenum; very rarely – abdominal pain, dyspepsia, stomatitis, tarry stools. Liver and biliary tract disorders: often-increased activity of “liver” enzymes; very rarely-hepatitis, fulminant hepatitis (including fatal outcomes), jaundice, cholestasis. Renal and urinary tract disorders: rarely-dysuria, hematuria, urinary retention; very rarely-renal failure, oliguria, interstitial nephritis. Disorders of water and electrolyte metabolism: rarely-hyperkalemia. Other: infrequently-peripheral edema; rarely-malaise, asthenia; very rarely-hypothermia.

Interaction

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding. Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, increase the risk of gastrointestinal bleeding. NSAIDs may enhance the effects of anticoagulants such as warfarin. Due to the increased risk of bleeding, this combination is not recommended and is contraindicated in patients with severe coagulation disorders. If combination therapy is still unavoidable, careful monitoring of blood clotting parameters is necessary. Diuretics: NSAIDs may reduce the effect of diuretics. In healthy volunteers, nimesulide temporarily reduces the excretion of sodium under the action of furosemide, to a lesser extent – the excretion of potassium, and reduces the actual diuretic effect.Concomitant use of nimesulide and furosemide results in a decrease (approximately 20%) in the area under the concentration – time curve (AUC) and a decrease in the cumulative excretion of furosemide without changing the renal clearance of furosemide. Concomitant use of furosemide and nimesulide requires caution in patients with renal or cardiac insufficiency. ACE inhibitors and angiotensin-P receptor antagonists: NSAIDs may reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), concomitant use of ACE inhibitors, angiotensin II receptor antagonists, and cyclooxygenase-suppressing agents (NSAIDs, antiplatelet agents) may lead to further deterioration of renal function and the occurrence of acute renal failure, which is usually reversible. These interactions should be considered in patients taking nimesulide in combination with ACE inhibitors or angiotensin II receptor antagonists. Therefore, concomitant use of these drugs should be carried out with caution, especially in elderly patients. Patients should receive sufficient fluids, and renal function should be carefully monitored after starting concomitant use. Theoretically, it is possible to reduce the effectiveness of mifepristone and prostaglandin analogues when used simultaneously with NSAIDs (including acetylsalicylic acid) due to the antiprostaglandin action of the latter. Limited data show that the use of NSAIDs on the day of use of a prostaglandin analog does not adversely affect the effect of mifepristone or a prostaglandin analog on cervical dilatation, uterine contractility, and does not reduce the clinical effectiveness of medical termination of pregnancy. There is evidence that NSAIDs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in blood plasma and its toxicity. When using nimesulide in patients undergoing lithium therapy, regular monitoring of the concentration of lithium in the blood plasma should be carried out. No clinically significant interactions were observed with glibenclamide, theophylline, igoxin, cimetidine, or antacids (for example, a combination of aluminum and magnesium hydroxides). Nimesulide inhibits the activity of the CYP2C9 isoenzyme. When drugs that are substrates of this enzyme are taken simultaneously with nimesulide, the concentration of the latter in plasma may increase. Caution should be exercised when prescribing nimesulide less than 24 hours before or after the use of methotrexate, as in such cases, the concentration of methotrexate in the blood plasma and, accordingly, toxic effects may increase. Due to the effect on renal prostaglandins, prostaglandin synthetase inhibitors, such as nimesulide, may increase the nephrotoxicity of cyclosporins.

How to take, course of use and dosage

Inside. The contents of the sachet are dissolved in approximately 100 ml of water at room temperature (a white or light yellow suspension is formed). The prepared solution is not subject to storage. The drug Nimesulide is used only for the treatment of patients over 12 years of age. Adults and children over 12 years of age: 1 sachet twice a day, after meals. Elderly patients: in the treatment of elderly patients, the need to adjust the daily dose is determined by the doctor based on the possibility of interaction with other drugs. Patients with renal insufficiency: in patients with mild to moderate renal insufficiency (creatinine clearance 30-60 ml/min), no dose adjustment is required, while in patients with severe renal insufficiency (creatinine clearance Patients with hepatic insufficiency: the use of the drug Animesulide in patients with hepatic insufficiency is contraindicated. To reduce the likelihood of side effects, it is recommended to take the minimum effective dose for as short a time as possible. The maximum daily dose for adults and children over 12 years of age is 200 mg. The maximum duration of treatment is 15 days.

Overdose

Symptoms: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible with symptomatic and supportive care. Possible increase in blood pressure, gastrointestinal bleeding, acute renal failure, respiratory depression, coma, anaphylactoid reactions. Treatment: Symptomatic and supportive therapy. There is no specific antidote. If an overdose has occurred within the last 4 hours, it is necessary to induce vomiting and/or provide activated charcoal (from 60 to 100 g for an adult) and / or an osmotic laxative. Forced diuresis, hemodialysis, hemoperfusion, and urinary alkalinization are ineffective due to the high degree of binding of nimesulide to plasma proteins (up to 97.5%). It is necessary to monitor the state of kidney and liver function.

Special instructions

Undesirable side effects can be minimized by using the drug at the lowest effective dose with the minimum duration of use necessary for the relief of pain. There are data on very rare cases of serious liver reactions, including cases of fatal outcome associated with the use of nimesulide-containing drugs. If you experience symptoms similar to those of liver damage (anorexia, pruritus, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of “liver” transaminases), you should immediately stop using Nimesulide and consult a doctor. Repeated use of the drug Animesulide in such patients is contraindicated. Liver reactions, which in most cases are reversible, have been reported with short-term use of the drug. During the use of Nimesulide, the patient should refrain from taking other analgesics, including NSAIDs (including selective COX-2 inhibitors). Nimesulide should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as these diseases may worsen. The risk of gastrointestinal bleeding, peptic ulcer/perforation of the stomach or duodenum increases in patients with a history of ulcerative lesions of the gastrointestinal tract (ulcerative colitis, Crohn’s disease), as well as in elderly patients, with an increase in the dose of NSAIDs, so treatment should begin with the lowest possible dose. Such patients, as well as patients who require concomitant use of low doses of acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, are recommended to take additional gastroprotectors (misoprostol or proton pump blockers). Patients with a history of gastrointestinal diseases, especially elderly patients, should inform the doctor about new gastrointestinal symptoms (especially those that may indicate possible gastrointestinal bleeding). Nimesulide should be used with caution in patients taking medications that increase the risk of ulceration or bleeding (oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid). If gastrointestinal bleeding or ulcerative lesions of the gastrointestinal tract occur in patients taking Nimesulide, treatment with the drug should be stopped immediately. Taking into account reports of visual impairment in patients taking other NSAIDs, if any visual impairment occurs, the use of Nimesulide should be stopped immediately and an ophthalmological examination should be performed. The drug may cause fluid retention, so in patients with arterial hypertension, renal and/or heart failure, Nimesulide should be used with extreme caution. If the condition worsens, treatment with Nimesulide should be discontinued. Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with prolonged use, may lead to a low risk of myocardial infarction or stroke. To exclude the risk of such events when using nimesulide, data are not sufficient. The drug can cause fluid retention in the body. Patients with arterial hypertension, renal and/or heart failure, ischemic heart disease, peripheral artery disease and/or cerebrovascular diseases, with the presence of risk factors for developing cardiovascular diseases (for example, hyperlipidemia, diabetes mellitus, in smokers), Nimesulide should be used with extreme caution. If the condition worsens, treatment with Nimesulide should be discontinued. The drug contains lactose monohydrate (milk sugar), this should be taken into account in patients with diabetes mellitus (0.14-0.16 XE per 100 mg of the drug) and persons who follow a low-calorie diet, the drug Nimesulide is not recommended for patients with lactose intolerance, lactase deficiency or glucose – galactose malabsorption syndrome. If signs of a “cold” or acute respiratory viral infection occur during the use of Nimesulide, the drug should be discontinued. Nimesulide can alter the properties of platelets, so caution should be exercised when using the drug in people with hemorrhagic diathesis, but the drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including the risk of life-threatening gastrointestinal bleeding and perforation, and reduced kidney, liver, and heart function. When taking the drug Nimesulide for this category of patients, proper clinical monitoring is necessary. There are reports of rare skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when taking NSAIDs, including nimesulide. At the first appearance of skin rash, mucosal lesions, or other signs of an allergic reaction, Nimesulide should be discontinued immediately.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Nimesulide

Conditions of release from pharmacies

By prescription

Dosage form

Oral suspension